Introduction <p>A prescribing cascade occurs when medication is used to treat or prevent an adverse drug reaction (ADR) to another medication. These prescriptions may contribute to problematic polypharmacy in people who are older. Research investigating potential prescribing cascades resulting in prochlorperazine prescription to treat non-steroidal anti-inflammatory drug (NSAID) or antihypertensive-induced dizziness or nausea is limited.</p> Aim <p>The aim of this study is to explore potential prescribing cascades resulting in prochlorperazine prescription after antihypertensive or NSAID initiation in community-dwelling Irish adults who are older.</p> Methods <p>Prescription sequence symmetry analysis was conducted on a pharmacy claims database of dispensed medications in Ireland (2017–2020) (<i>n</i> = 514,056). Participants (aged ≥ 65 years) were included if they met General Medical Services Scheme eligibility and were incident users of either exposure medication—(i) antihypertensives (alpha adrenoreceptor blockers, beta blockers, calcium channel blockers, diuretics, angiotensin receptor blockers, angiotensin-converting enzyme inhibitors) or (ii) NSAIDs—and the potential cascade medication, prochlorperazine. The primary observation window was 365 days. Crude and adjusted sequence ratios with 95% confidence intervals (CI) were calculated. Stratified analyses of observation window time, sex and individual medications were conducted.</p> Results <p>Significant positive associations were identified for antihypertensives and NSAIDs leading to subsequent prochlorperazine prescription. Adjusted sequence ratios (aSR) ranged from 1.27 (95% CI 1.16–1.40) for all diuretics to 1.81 (95% CI 1.49–2.19) for urological alpha adrenoreceptor blockers. The prevalence of each medication dyad ranged from 1.04% for urological alpha adrenoreceptor blockers to 1.38% for cardiac alpha adrenoreceptor blockers. The magnitude of positive associations was slightly attenuated for all dyads when the observation window was reduced to 180 and 60 days, although almost all of these remained significant. Results varied by sex and individual medication. The beta-blocker-to-prochlorperazine dyad had an aSR of 1.94 (95% CI 1.60–2.36) for male patients and 1.45 (95% CI 1.27–1.66) for female patients.</p> Conclusions <p>NSAID and antihypertensive-induced ADRs such as dizziness or nausea may contribute to subsequent prochlorperazine initiation among adults who are older, representing a potential prescribing cascade. Further research examining data that include clinical indications for prescribing is needed to confirm whether these signals represent true prescribing cascades or prescribing for another reason. ADRs should be included in the differential diagnosis for people who are older presenting with new symptoms in primary care.</p>